A decline in motor performance contributes to laryngeal dysfunction in the elderly. However, improved methods of prevention, diagnosis and treatment of age-related laryngeal dysfunction will require identification of the basic pathogenic mechanisms underlying age-related cell death and remodeling of the highly specialized muscles of the larynx. Stereological studies on a laryngeal adductor, the thyroarytenoid muscle, have demonstrated an aging process that differs from most other skeletal muscles, but comparable data is lacking for other laryngeal muscles. This project will provide the first statistically unbiased quantitative data concerning age-related cell death and pathogenic mechanisms underlying age-related remodeling of the human posterior cricoarytenoid muscle (PCA), the laryngeal abductor. The PCA is adapted to its crucial inspiratory role with fatigue resistant muscle fiber types, which have an extremely high mitochondrial content and a very high blood flow. These characteristics may contribute to the reported early aging of this muscle. It is likely that this specialization for oxidative capacity is interdependent with mechanisms that regulate the myonuclear cytoplasmic domain, which underlie the control of muscle fiber size and strength. Furthermore, these extreme adaptations for oxidative metabolism require very high blood flow rates. Little is known about laryngeal blood flow or its controlling mechanisms and even less about the influence of age on these variables. It is not technically feasible to obtain absolute blood flow measurements directly from human subjects. However, it is possible to make inferences about blood flow and its control mechanisms based on vascular morphology and the identification of the types and densities of vascular innervation. The proposed studies will use stereological techniques to provide quantitative three-dimensional data regarding the role of the following parameters in the pathogenic mechanisms underlying age-related remodeling of the human PCA: 1) Changes in numerical densities of myonuclei and satellite cells in type 1 and type 2 muscle fibers; 2) Changes in the numerical densities and percentages of apoptotic myonuclei and apoptotic satellite cells in type 1 and type 2 muscle fibers; 3) Changes in the content of regenerating muscle fibers; 4) Changes in the length density of vascular elements; 5) Changes in the pattern or types of vascular innervation and their length densities and 6) Changes in the numerical densities and percentages of apoptotic endothelial cell nuclei. The proposed studies will provide data concerning the basic mechanisms underlying age-related remodeling of the human PCA. Since processes such as apoptosis are potential targets for clinical intervention, the proposed studies will be essential to the design of improved strategies for the prevention or treatment of age-related laryngeal dysfunction.